Format

Send to

Choose Destination
Biochem Pharmacol. 1992 Apr 1;43(7):1649-53.

Optimal detergent activation of rat liver microsomal UDP-glucuronosyl transferases toward morphine and 1-naphthol: contribution to induction and latency studies.

Author information

1
Départment de Recherche sur la Sécurité du médicament, Rhône-Poulenc Rorer, Vitry sur Seine, France.

Abstract

The detergent-activation profiles of UDP-glucuronosyl transferases (UGTs, EC 2.4.1.17) toward 1-naphthol and toward morphine have been determined: three non-ionic detergents, Triton X-100, Brij 58 and Lubrol Px and one zwitterion detergent, 3-(3-cholamidopropyl)-dimethylammonio-1-propanesulfonic acid (CHAPS) were studied. The results showed that marked inhibition of 1-naphthol-UGT and morphine UGT activities occurred with high concentrations of Triton X-100. Lubrol Px, at high concentrations, inhibited 1-naphthol-UGT but not morphine-UGT. It appeared that the detergent/protein ratio suitable for optimal activation of both isoenzymes was limited to 0.2 for these detergents. In contrast, Brij 58 and CHAPS displayed optimal activation of the two enzymes for a large range of detergent/microsomal protein ratios (respectively from 0.2 to 1 and from 0.4 to 1), making them the most suitable for induction and/or latency studies of both isoenzymes. The influence of maximal activation status on the effect of 3-methylcholanthrene and phenobarbital treatment on morphine-UGT and 1-naphthol-UGT activity has also been evaluated. The findings provided evidence that detergent-activation profiles and optimal detergent-activated versus "native" UGT activity determination give crucial informations about the characteristics of a given isoenzymic form of UGT, i.e. its sensitivity to specific alterations of the phospholipid environment, its latency and its inducibility.

PMID:
1567486
DOI:
10.1016/0006-2952(92)90225-8
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center